1. Field of the Invention
The present invention relates to a method for preparing a propargylic alcohol catalyzed by 2-morpholinoisobornane-10-thiol (MITH).
2. Description of Related Art
Chiral propargylic alcohols are versatile building blocks for the synthesis of optically active pharmaceutical ingredients and natural products. The following Table 1 exemplifies some applications of propargylic alcohols.
TABLE 1EntryStarting blockSynthetic productRemark1Chondrillin, an anticancer natural product 2Pesticide 3(−)-Chlorothricolide, an aglycone of chlorothricin which is an antibiotic capable of inhibiting biosynthesis of cholesterol 4(+)-Spirolaxine, isolated from fungi, being able to reduce the amount of cholesterol, and toxic to endothelial and tumor cells 5(−)-Scopadulcic Acid A, extracted from Scrophularia L., being helpful to digestion and protective to digestive system
Among the several efficient procedures that have been developed, such as Ti-mediated reactions, there is a particular emphasis on the asymmetric nucleophilic addition of Zn-alkynylides to carbonyl compounds to prepare enantioenriched propargylic alcohols, which offer the advantages of the low-toxicity of zinc metal and the wide functional group tolerance of organozinc reagents. In literature reports describing the asymmetric addition of Zn-alkynylides to aldehydes, preparing the corresponding propargylic alcohols in high enantiomeric excess (ee) usually requires high ligand loadings. Thus, it is desirable to develop a method for preparing propargylic alcohols with an effective chiral mediator that promotes the enantioselective alkynylation of aldehydes at lower ligand loading.